SHBG Misconceptions

[galaxy]

With all the emphasis placed on the importance of SHBG and the free hormones I was wondering what people thought about the article below. Apologies if this has already been posted /discussed.

Sex Hormone Binding Globulin: New Science Questions Old Beliefs

 

[ERO]

This makes perfect sense to those of us with very low SHBG. Conventional wisdom would indicate that lower is better, when in fact low SHBG means that one will often get no real benefits from TRT. My SHBG was 12 at my last test and Testosterone to me feels like I am injecting water. Oh, and I am not obese, pre-diabetic or diabetic.

 

[Whatzup]

This makes perfect sense to those of us with very low SHBG. Conventional wisdom would indicate that lower is better, when in fact low SHBG means that one will often get no real benefits from TRT. My SHBG was 12 at my last test and Testosterone to me feels like I am injecting water. Oh, and I am not obese, pre-diabetic or diabetic.

I have low shbg 15-17 tested only twice and when I was using transdermal I had a TT level of 750-850 and FT 18-25 or so with sensitive E2 test of 27-29 without a blocker and all was good. I just started shots because I was tired of applying the cream and afraid of transfer. I recently started shots and haven't had labs yet. Guys here mention us low shbg guys need every other day shots or daily. I am doing every 5 days until I get labs. I am sure though the guys here are correct from experience that more frequent shots are better for us. I am just going to wait for my first set of labs.

How often do you inject?

 

[blackebob]

whatzup, I switched from cream 9 monthss ago, and I inject daily. My SHGB runs under 20, last time it was 17. good luck on the switch, I have been fighting water retention from day one of the shots.

 

[Vince Carter]

whatzup, I switched from cream 9 monthss ago, and I inject daily. My SHGB runs under 20, last time it was 17. good luck on the switch, I have been fighting water retention from day one of the shots.

ARe you using the "Estradiol, Free" testing and not just the LC/MS/MS?

 

[blackebob]

Quest ultra sensitive, and the free E.

 

[Vince Carter]

Quest ultra sensitive, and the free E.

what kind of numbers are you running if I may ask? Elevated E and water retention is why I ask.

 

[ERO]

I have low shbg 15-17 tested only twice and when I was using transdermal I had a TT level of 750-850 and FT 18-25 or so with sensitive E2 test of 27-29 without a blocker and all was good. I just started shots because I was tired of applying the cream and afraid of transfer. I recently started shots and haven't had labs yet. Guys here mention us low shbg guys need every other day shots or daily. I am doing every 5 days until I get labs. I am sure though the guys here are correct from experience that more frequent shots are better for us. I am just going to wait for my first set of labs.

How often do you inject?

I used to inject small amounts daily (for 2 years) but that makes no difference (to me) in how I feel so I am back to E3.5 days. I don't clear Test from my system super fast like a lot of low SHBG guys do.

 

[blackebob]

July labs were without an AI, I was fighting my blood pressure. September was with. After September draw I reintroduced HCG, And after my second injection I put on 12lbs of water, and my E shot through the roof. I couldnt get it tested for 2 weeks. When I did test,i t was sitting at 31, she didnt call in the free E test. When it shot up I added back in the calcium d glucaeate, and DIM along with the AI, and the symptons have gone away. I liked the HCG Add though, it was a nice bump in libido. I wish I could figure out how to keep the water off. I was taking .26 mg Test Cyp daily with .5mg AI E/3D at latest labs. I decided to drop it down to.24 mg and after next labs I might drop it down to .20mg Tto see if it works bettor with my low SHBG.500 Calcium D,and 350 DIM twice daily.
Thoughts?
September July

SHBG 16 17
FREE T 317 282
Bio T 667 581
T 1151 1067
Utra E 21 68
Free E .57 1.25

sorry it wont let me space the numbers apart

 

[galaxy]

Given the article is fairly lengthy I've excerpted a portion. This seems to indicate that a simplistic approach of free hormones and SHBG may not be accurate.

Taken together, the body of research on SHBG’s multiple functions puts the biomarker’s level fluctuations into context. That Joe has a SHBG level of 50 nmol/L level and Jeff has 30 nmol/L and both have the same plasma testosterone concentration (in the optimal range) does not necessarily mean that Jeff is better off due his higher free testosterone. That’s because tissue distribution of both RSHBG, megalin, as well as the presence of SHBG glycosylation variants all factor into the ability of testosterone to enter various responsive tissues and the plasma clearance of the steroid.

Thus, SHBG is a multifunctional player that can orchestrate steroid action to a degree far greater than that attributed to it just through its binding ability, so I think it’s safe say that the free hormone hypothesis is a myth, at least in its absolute sense

 

[Vestpocket]

The free hormone hypothesis is indeed a myth and based on very old studies with limited in vitro tissue samples. However, that's true for most hormone research.

In men on TRT, low SHBG will increase free diffusion through cell membranes, but accelerate hepatic metabolic clearance and reduce intracellular and extracellular AR signalling. In one study, for example, human androgen dependent prostate cancer cells respond to SHBG+T better than they do to pure free T. Why? SHBG is brought into a cell via the extracellular megalin receptor, where it is used to prolong the activity of steroid molecules within a cell. Without SHBG, free testosterone is rapidly glucuronidated and effluxed from the cell. SHBG and T work in concert.

The literature provides us with a case of a totally SHBG deficient male. His complaints were low libido and low musculature, even though he was otherwise fully androgenized. These complaints were not remedied with testosterone supplementation. The study authors concluded that a tissue dependent effect of SHBG on androgenic signalling was proven. The doctors treating the 0-SHBG patient gave up on testosterone replacement and decided to pursue methods of increasing his overall energy level.

It appears, thus, that SHBG is required in sufficient amounts in tissues like muscle that require a very high level of androgen signalling.

Moreover, there is an extracellular receptor for SHBG that requires SHBG to be unoccupied by a hormone to bind. Once bound, it catches a free steroid molecule and completes the extracellular AR signalling pathway. If SHBG is low, this activity can be nearly completely inhibited.

One interesting thing to note is that on a protien-per-molecule level, SHBG and testosterone are produced in nearly identical quantities. The molecular weights of testosterone versus SHBG are very different, but by serum concentration, a healthy male produces slightly more SHBG than he does testosterone. This is actually required for proper hormone balance and function.

There are no studies that show an independent effect of free testosterone elevation on musculature. This is pure conjecture based on ill-informed "broscience" mythology. In all studies where testosterone positively correlates with lean tissue growth, total testosterone is increased proportionately to SHBG and FT% is within the normal range.

If we look for a case of testosterone administration with low SHBG and a therefore excessively free testosterone percentage, and expect to see better "results in the gym" -- we will not. We have not.

 

[Vince Carter]

The literature provides us with a case of a totally SHBG deficient male. His complaints were low libido and low musculature, even though he was otherwise fully androgenized. These complaints were not remedied with testosterone supplementation. The study authors concluded that a tissue dependent effect of SHBG on androgenic signalling was proven. The doctors treating the 0-SHBG patient gave up on testosterone replacement and decided to pursue methods of increasing his overall energy level.

Elaborate on how in this instance the authors delved in to Estrogen/Free Estrogen management, treatment outside of T replacement (not supplementation).

You can't.

See, this garbage is always suspect...it's not supplementation. It's replacement. No mention of how any one tried to treat this guy's E, just give him T and give up and say it's an SHBG problem. Its highly suspect how you're just regurgitating what you think you read somewhere, (no link), passing it off as factual when every day on the forum(s) you can be found to be about as wrong as wrong can be.